Multi-agent combination chemotherapy can be curative in acute lymphoblastic leukemia (ALL). Still, patients with primary refractory disease or with relapsed leukemia have a very poor prognosis. Here we integrate an in-depth dissection of the mutational landscape across diagnostic and relapsed pediatric and adult ALL samples with genome-wide CRISPR screen analysis of gene-drug interactions across seven ALL chemotherapy drugs. By combining these analyses, we uncover diagnostic and relapse-specific mutational mechanisms as well as genetic drivers of chemoresistance. Functionally, our data identifies common and drug-specific pathways modulating chemotherapy response and underscores the effect of drug combinations in restricting the selection of resistance-driving genetic lesions. In addition, by identifying actionable targets for the reversal of chemotherapy resistance, these analyses open novel therapeutic opportunities for the treatment of relapse and refractory disease.Introduction Klebsiella is a clinically important pathogen causing a variety of antimicrobial resistant infections in both community and nosocomial settings, particularly pneumonia, urinary tract infection, and sepsis. Bacteriophage (phage) therapy is being considered a primary option for the treatment of drug-resistant infections of these types. Methods We report the successful isolation and characterization of 30 novel, genetically diverse Klebsiella phages. Results The isolated phages span six different phage families and nine genera, representing both lysogenic and lytic lifestyles. Individual Klebsiella phage isolates infected up to 11 of the 18 Klebsiella capsule types tested, and all 18 capsule-types were infected by at least one of the phages. Conclusions Of the Klebsiella-infecting phages presented in this study, the lytic phages are most suitable for phage therapy, based on their broad host range, high virulence, short lysis period and given that they encode no known toxin or antimicrobial resistance genes. Phage isolates belonging to the Sugarlandvirus and Slopekvirus genera were deemed most suitable for phage therapy based on our characterization. https://www.selleckchem.com/products/Dapagliflozin.html Importantly, when applied alone, none of the characterized phages were able to suppress the growth of Klebsiella for more than 12?h, likely due to the inherent ease of Klebsiella to generate spontaneous phage-resistant mutants. This indicates that for successful phage therapy, a cocktail of multiple phages would be necessary to treat Klebsiella infections.Soil biogeochemical cycles and their interconnections play a critical role in regulating functions and services of environmental systems. However, the coupling of soil biogeochemical processes with their mediating microbes remains poorly understood. Here, we identified key microbial taxa regulating soil biogeochemical processes by exploring biomarker genes and taxa of contigs assembled from metagenomes of forest soils collected along a latitudinal transect (18° N to 48° N) in eastern China. Among environmental and soil factors, soil pH was a sensitive indicator for functional gene composition and diversity. A function-taxon bipartite network inferred from metagenomic contigs identified the microbial taxa regulating coupled biogeochemical cycles between carbon and phosphorus, nitrogen and sulfur, and nitrogen and iron. Our results provide novel evidence for the coupling of soil biogeochemical cycles, identify key regulating microbes, and demonstrate the efficacy of a new approach to investigate the processes and microbial taxa regulating soil ecosystem functions.Since the first invention of triboelectric nanogenerators (TENGs) in 2012, many mechanical systems have been applied to operate TENGs, but mechanical contact losses such as friction and noise are still big obstacles for improving their output performance and sustainability. Here, we report on a magnet-assembled cam-based TENG (MC-TENG), which has enhanced output power and sustainability by utilizing the non-contact repulsive force between the magnets. We investigate the theoretical and experimental dynamic behaviors of MC-TENGs according to the effects of the contact modes, contact and separation times, and contact forces (i.e., pushing and repulsive forces). We suggest an optimized arrangement of magnets for the highest output performance, in which the charging time of the capacitor was 2.59 times faster than in a mechanical cam-based TENG (C-TENG). Finally, we design and demonstrate a MC-TENG-based windmill system to effectively harvest low-speed wind energy, ~4?m/s, which produces very low torque. Thus, it is expected that our frictionless MC-TENG system will provide a sustainable solution for effectively harvesting a broadband of wasted mechanical energies.Electrochemistry, one of the most important research and production technology, has been widely applicated in various fields. However, the requirement of external power source is a major challenge to its development. To solve this issue, developing self-powered electrochemical system (SPES) that can work by collecting energy from the environment is highly desired. The invention of triboelectric nanogenerator (TENG), which can transform mechanical energy into electricity, is a promising approach to build SPES by integrating with electrochemistry. In this view, the latest representative achievements of SPES based on TENG are comprehensively reviewed. By harvesting various mechanical energy, five SPESs are built, including electrochemical pollutants treatment, electrochemical synthesis, electrochemical sensor, electrochromic reaction, and anticorrosion system, according to the application domain. Additionally, the perspective for promoting the development of SPES is discussed.Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction between the primers and the respiratory swab RNA extracts, based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). To achieve clinically acceptable performance, we synthesized a group of six primers to identify the conserved regions of the ORF1ab gene of SARS-CoV-2. Clinical trials were conducted with 87 PCR-positive and 43 PCR-negative patient samples. The platform demonstrated both high sensitivity (95.40%) and high specificity (95.35%), showing potentials for rapid and user-friendly diagnosis of COVID-19 among many other infectious pathogens.